SEC61G Facilitates Brain Metastases via Antagonizing PGAM1 Ubiquitination and Immune Microenvironment Remodeling in Non-Small Cell Lung Cancer

Abstract

In conclusion, this study identifies a novel mechanism in which SEC61G drives NSCLC brain metastases by competitively inhibiting UBE3C-mediated ubiquitination of PGAM1, stabilizing PGAM1 and enhancing glycolysis. In addition to metabolic reprogramming, SEC61G impairs TLS maturation, suppresses adaptive immune responses, and facilitates immune evasion, contributing to brain metastatic colonization. These findings highlight SEC61G as a key regulator of brain metastasis and a promising therapeutic target for NSCLC patients with brain metastases.